The initiation of diverse pathways of tissue differentiation along the dorsal-ventral (D-V) body axis of the early Drosophila embryo is controlled by a maternal morphogen called dorsal (dl). The long term goal of the proposed study is to determine how this morphogen gradient differentially regulates gene expression along the D-V axis. dl is a novel sequence-specific DNA binding protein that shares extensive homology with the mammalian rel and NF-kB regulatory factors. Peak levels of dl activate two target genes called twist and snail, which encode regulatory factors responsible for the differentiation of the ventral mesoderm. The two genes are expressed in overlapping, but noncoincident patterns due to their differential activation by the dl morphogen. A major goal of this study is to determine how small changes in the levels of the dl morphogen specify these distinct limits of gene expression. dl also influences cell fate by repressing gene expression, and is responsible for restricting the activities of the homeobox gene zerknullt (zen) to dorsal regions where it directs the differentiation of the amnioserosa. There are several dl binding sites in the zen promoter, and their activities will be evaluated using a combination of in vitro mutagenesis and P-transformation assays. Genetic studies will be done to determine whether regulatory factors responsible for the differentiation of the neuroectoderm are directly influenced by the dl morphogen. Finally, the proposed study will include the molecular characterization of a novel regulatory gene responsible for the differentiation of the dorsal epidermis, called screw.